Introduction

Little is known on the outcomes of endoscopic submucosal dissection (ESD) in patients with recurrent lesions after surgical local excision (transanal endoscopic surgery TES, transanal endoscopic microsurgery TEM, transanal minimally invasive surgery TAMIS) of superficial rectal neoplasms (1). We aimed to evaluate the feasibility, safety and efficacy of ESD for incomplete or recurrent rectal neoplastic lesions after transanal surgery.

Aims & Methods

This multicenter retrospective study assessed 38 patients who underwent ESD between June 2016 and February 2022 for recurrent or incompletely resected after TES or TEM. Treatment outcomes were evaluated. Primary outcome was the non-recurrence tumoral lesion at first endoscopic follow-up control. Secondary outcome were En bloc resection, R0 resection, curative resection.

Results

Main results are given in Table 1. There were 16 male and 22 female patients. Median age (range) was 68.7 (44–88) years. Seventy-four percent of lesions were located in the lower rectum, and 55% reached the pectineal line. Sixty-one percent of lesions were laterally spreading tumor granular type (LST-G), and 34% were polyps. Forty-four percent of lesions were 0-IIa, and 23% were 0-Is according to the Paris classification. Seventy-one of lesions were Sano II, and 45% of lesions were Kudo IV. The median size of lesions (range) was 44 mm (10-100). Sixty-six percent of ESD were performed starting with full circumferential incision. Median operation time (range) was 79 (10–270) minutes. Thirty-nine percent of lesions has low vascular supply. Severe fibrosis was present in 78%of lesions. Ninety-two percent of lesions were successfully resected en bloc. R0 resection and curative resection rates were both 68%. Rectal fat is visualized in eleven patients, none of them requiring a surgery. Four post-operative bleeding and two stenosis occurred. Median (range) hospital length of stay after ESD was 1.8 days (0-4). Pathological examination revealed 32 adenomas (23 with low-grade dysplasia, 9 with high-grade dysplasia) and 3 adenocarcinomas (3 T2; there was no Tis or T1). All patients were followed up with endoscopic control after ESD, with biopsy samples if residual or recurrent tumor.Median (range) of follow-up period until first endoscopy control was 6.2 (1-13) months. « Only one residual lesion (one of three non-en bloc resections) actually showed low-grade dysplasia adenoma at follow-up.

Conclusion

ESD for incomplete or recurrent superficial rectal neoplastic lesions after transanal surgery (TEM,TES, TAMIS) is highly feasible and safe, and allows curative resection in a vast majority of cases.

References

1) Ikezawa N, et al. Digestion. 2021;102(3):446‑52.

Introduction

Endoscopic submucosal dissection (ESD) and transanal minimally invasive surgery (TAMIS) are considered standard of care minimally invasive local en bloc resection techniques for larger benign rectal polyps and early-invasive rectal cancer. To optimize post-procedural care for patients, it is important to obtain more insight in the post-procedural physical recovery of both techniques.

Aims & Methods

This is an ancillary study of the multicenter non-inferiority randomized TRIASSIC-trial (Netherlands Trial Register: NL7083) that compares the outcomes of ESD and TAMIS for large (≥20mm) rectal polyps (1). Patients were 1:1 randomized between ESD or TAMIS and monitored with a smartwatch during a 14-day baseline period prior to resection and a 28-day post-procedural recovery period. A mixed-effects model was fitted for physical activity to describe the recovery period. Recovery was defined as reaching ≥90% of the baseline step-count for 2 consecutive days. If patients did not meet this pre-defined definition of recovery within 28 days post-treatment, a recovery time of 30 days was used in the analyses. This study analyzed subjective time to recovery through an end-of-study questionnaire and post-procedural pain through a self-reported pain diary.

Results

A total of 40 patients were included (20 ESD, 20 TAMIS). The mean age was 66.7 years (SD 7.4), 57.5% was male, and median polyp size was 42.5mm (IQR 25). Histological assessment showed a benign polyp in 82.5% and early-stage T1 rectal cancer in 17.5%. Seventeen patients (85%) in the ESD group and 15 patients (75%) in the TAMIS group were physically recovered within the 28-day post-procedural recovery period (p=0.43). The median time to physical recovery was 6.5 days (IQR 18) after ESD and 14.5 days (IQR 21.3) after TAMIS (p=0.022). Subjective time to recovery was 1-2 weeks in 47.5%, 3-4 weeks in 17.5%, and 32.5% did not feel completely recovered within 28 days. There was a significant correlation (Spearman’s rho = 0.66, p<0.001) between the physical (smartwatch) and subjective (end-of-study questionnaire) time to recovery. Post-procedural pain scores in the first week were similar between ESD and TAMIS (p=0.86) and were significantly associated with patients’ level of physical activity (p<0.01); for each point increase in the pain score total step count compared to baseline decreased by 14% after both ESD (95%CI 4-22%) and TAMIS (95%CI 5-22%). Additionally, higher post-procedural pain scores were significantly associated with a prolonged time to recovery (p=0.001). Other factors that were significantly associated with a prolonged time to physical recovery were polyp diameter ≥4cm (only in the ESD group; p=0.003), polyp located ≤1cm from the dentate line, and female sex (only in the TAMIS group, p=0.02 and p=0.03, respectively)

Conclusion

ESD-treated patients have a shorter physical recovery time of ~1 week as compared to ~2 weeks for TAMIS-treated patients. Post-procedural pain is a potentially modifiable factor that significantly influences physical activity and time to physical recovery after ESD and TAMIS.

References

1. Dekkers N, Boonstra JJ, Moons LMG, Hompes R, Bastiaansen BA, Tuynman JB, et al. Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial. BMC Gastroenterology. 2020;20(1):225.

Disclosure

The TRIASSIC trial is funded by ZonMW (Efficiency program: 852001926) and Applied Medical. Funding bodies had no role in the study design, data collection and analyses, decision to publish, or preparation of this abstract.

Introduction

Collagenous colitis (CC) is a form of microscopic colitis (MC), the others being lymphocytic colitis (LC), incomplete CC and incomplete LC (1). It is an inflammatory disease of the large bowel that causes chronic watery diarrhoea, abdominal pain, faecal incontinence, nightly defecation, and weight loss, resulting in significantly impaired quality of life (2). Incidence of MC has increased significantly during the past decades in some countries and the main reason for this increase is thought to be an enhanced disease recognition (3). The diagnosis of MC is challenging as it can only be diagnosed upon histological examination of colonic biopsies taken from normal or near normal appearing mucosa (1). Histological interpretation of biopsies involves subjective evaluation leading to inter-rater variability discrepancies in diagnosis and treatment plan. Deep learning-based assistance system can objectivise diagnostic key feature selection leading to minimisation of inter-rater variability and improvement of diagnostic accuracy.

Aims & Methods

The aim of this pilot study was to develop an algorithm for robust segmentation of light microscopy images of histological specimen slides (tissue slides) emphasizing key diagnostic features of CC.
Histological specimens were fixed with formalin, embedded in paraffin, cut into 3 µm sections, and stained with haematoxylin and eosin (H&E) for histological examination. Images were taken using OLYMPUS IX71 light microscope (x20 magnification) equipped with Q IMAGING EXI aqua camera at (1392 x 1040 pix.) resolution and 24-bit pixel encoding. Registered image pixel values were normalized in RGB colour space by histogram alignment using empty tissue-less areas using an algorithm described previously (4). Superpixel technique using Simple Linear Iterative Clustering algorithm (5) was used for initial segmentation of the images. All 1000 superpixels defined in each image were annotated by the expert, indicating ones containing thickened subepithelial collagen layer as the sought class among the others containing the rest of the tissue indicated as normal class. The feed – forward neural network (implemented in MatLab environment) was trained to classify superpixels using their normalized histogram bin-counts of the pixel values as a feature. Due to significant inequality in the data set, where the number of sought class superpixels was significantly smaller than the number of the remaining ones, the training set was formed by equalising it to the lowest class case’s value (18761). Only randomly selected cases of the bigger class were included in the training set.

Results

The proposed algorithm was tested on images from 5 treatment-naive patients with newly diagnosed CC. Patients' histological specimens were rated by an expert pathologist and 50 images were chosen (with changes characteristic of CC and without). The classification training process with extracted data set took 0.13 seconds on personal computer with an AMD Ryzen Threadripper 3970X 32-Core, 3.70 GHz processor and 128GB of RAM memory, epochs for training was set to 30 (after tests the model was not improving after 30 epochs) and data shuffling was set to every-epoch. The algorithm showed 0.807 accuracy, 0.801 sensitivity and 0.813 specificity.

Conclusion

The shown ability of deep learning algorithm to classify histology image segments can assist the diagnostic process of CC emphasizing thickened subepithelial collagen layer – the essential diagnostic feature.

References

1. Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Fiehn AMK, Wildt S, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterol J. 2020;
2. Verhaegh BPM, Münch A, Guagnozzi D, Wildt S, Cebula W, Diac AR, et al. Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study. J Crohns Colitis. 2021;15(7):1174–83.
3. Weimers P, Ankersen DV, Lophaven S, Bonderup OK, Münch A, Løkkegaard ECL, et al. Incidence and Prevalence of Microscopic Colitis between 2001 and 2016: A Danish Nationwide Cohort Study. J Crohns Colitis. 2021;14(12):1717–23.
4. Petrolis R., Čižas P., Borutaitė V., Kriščiukaitis A. Method of fluorescence imaging for evaluation of membrane potential in cultured neurons using transmembrane voltage sensitive dye. Biomedical engineering 2011: Proceedings of International Conference. 14:16-19, 2011.

5. Achanta R, Shaji A, Smith K, Lucchi A, Fua P, Susstrunk S. SLIC Superpixels Compared to State-of-the-art Superpixel Methods. IEEE Transactions on Pattern Analysis and Machine Intelligence, Volume 34, Issue 11, pp. 2274-2282, May 2012

Clinical Case Summary

An hemoperitoneum may be the initial presentation of a liver tumour. A good differential diagnosis is critical, including trauma, vascular rupture and tumours.
A 79-year-old male, retired welder and painter, consulted for weight loss, abdominal pain and distension of 3 months of evolution. Ascitic semiology led to do a paracentesis with hematic debit. An urgent computerized tomography (CT) reported hemoperitoneum secondary to multicentric liver tumor with active bleeding (Figure 1) and intratumoral pseudoaneurysms compatible with angiosarcoma, performing an urgent transarterial embolization (Figure 2). Extension CT ruled out distant disease, magnetic resonance imaging (MRI) was realized (Figure 3) and fine needle aspiration (FNA) showed atypical cellular with CD31 expression (Figure 4), consistent with primary hepatic angiosarcoma (PHA). Given the bilobar involvement, surgery was dismissed and he was treated with chemotherapy (CTX), dying at 10 months of diagnosis.
PHA is a rare entity (2% of primary liver tumor) with an annual prevalence of 200 worldwide cases and a male predominance (3:1) at 60 years. It has been associated to exposure to vinyl chloride, arsenic or thoracotrast, but currently 75% of diagnoses have unknown aetiology.
Diagnosis is based on anatomopathology and inmunohistochemistry, including atypical cellularity in FNA and expression of vascular markers as ERG (100%), CD34 (87%) and CD31 (79%). Imaging tests are non-specific, with hypodense lesions in CT and T2-weighted hyperintense sequence in MRI.
Due to its aggressiveness, around 60% of PHA presents lymph nodes or lung, bones or spleen metastases at diagnosis. Liver resection is the only potentially curative treatment because it is a radioresistent tumour. Transplantation is not recommended due to its high recurrence rate. PHA has less than 6 months of overall survival (OS) without treatment. Otherwise, patients with CTX treatment has a OS of 3% at 2 years of diagnosis.

Introduction

The Updated Sydney System recommends reporting the severity of both glandular atrophy (GA) and intestinal metaplasia (IM) as two independent parameters. However, the OLGA system assesses both GA and IM together as part of the same entity which should be reported as an average severity. The OLGIM system is based on the IM severity recommended by the updated Sydney system. Thus, the final OLGIM score can be estimated by any clinician. Currently, no system addresses the severity of both GA and IM as they are reported following the updated Sydney recommendation.

Aims & Methods

This study aimed to assess the utility of a new system, OLGIMA (Operative Link on Gastric IM and GA assessment), as a tool to identify patients at higher risk for GC in daily practice.
Consecutive diagnostic UGI endoscopies performed for any indications in patients older than 18 years old were recorded prospectively in 21 Spanish hospitals between April 2021 and July 2023. Protocolized gastric biopsies were taken according to the Updated Sydney consensus. We excluded patients with dysplasia, any malignancy, suspicion of autoimmune chronic atrophic gastritis, and lack of histological data. The severity of both GA and IM was assessed in the antrum (including incisura) and corpus following the updated Sydney system. After that, we considered the most advanced severity (none:0; mild:1; moderate:2; marked:3) provided for any of them in each of the two topographical areas. Then, the OLGIMA staging was done according to the same methodology used by the OLGA and OLGIM systems.

Results

A total of 998 patients were included. The median age was 57 (IQR 46 - 67), and 64% were women. Hp infection was identified in 334 (35%) patients (19% active infection and 16% eradicated). GA was identified in 192 (19.2%) patients which was limited to the antrum in 113 (11.3%) cases and extensive in 79 (7.9%). IM was identified in 159 (15.9%) patients which was limited to the antrum in 114 (11.4%) cases and extensive in 45 (4.5%). According to IM severity, 27 (2.7%) patients were OLGIM III/IV. According to GA severity, 22 (2.2%) patients were significantly extensive. The OLGIM system would have missed 12 (1.2%) patients with GA at higher risk. Considering both criteria, we would have detected 39 (3.9%) patients at higher risk in total (17 OLGIM III-IV, 12 extensive significative GA, and 10 both OLGIM III-IV and extensive significative GA). The new OLGIMA system categorized all 39 (3.9%) patients, OLGIM III-IV and significantly extensive GA, in the high-risk group (OLGIMA III/IV).

Conclusion

The new OLGIMA system (based on the severity of IM and GA recommended by the updated Sydney system) was able to detect patients at higher risk including all cases of OLGIM III/IV and also with advanced GA. The OLGIMA staging is much simpler and it can be estimated by any clinician regardless of whether the biopsy from incisura was taken.

References

Rugge M, Meggio A, Pennelli G et al. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6
Capelle LG, de Vries AC, Haringsma J et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8
Pimentel-Nunes P, Libânio D, Marcos-Pinto R et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51:365-388.

Introduction

In a previous case study, we reported the use of endoscopic band ligation for weight loss (1). Based on this, we performed the same procedure on 13 female cases.

Aims & Methods

This trial aimed to assess the efficacy and safety of endoscopic band ligation for weight loss among 13 female cases with initial body weight (kg) mean ± SD of 104.769 ± 17.316 (80–145), BMI mean ± SD of 40.4315 ± 4.9145 and a mean excess weight (kg) of 40.0769 ± 14.3669, Table 1.
For the endoscopy, the patients were sedated with propofol, and oxygen was used for endoscopic air insufflation. The ligatures were applied in the gastric body, starting distally; five parallel rows were created with 20–30 bands, with the last one placed in the proximal body. The entire procedure lasted 20–30 min.

Results

No immediate complications occurred during the endoscopy. After the procedure, the patients remained well and were discharged within 2–3 h. For the first three days, most complained of nausea, vomiting, and epigastric pain, and one patient experienced mild hematemesis. All complications were controlled with medications (pantoprazole 40 mg twice daily for the 1st month, plus antiemetics and antispasmodics as required).
The patients consumed a pureed diet for 2 weeks, followed by a soft diet for another 2 weeks. A follow -up endoscopy after 1 month revealed nicely healed ulcer scars in the gastric body, causing marginal narrowing of the lumen.
The patients’ weight loss (kg) was mean ± SD 96.6154 ± 16.8004, corresponding to 22.336% excess weight loss and 7.8752% total weight loss after 1 month, Table 2.

Conclusion

Endoscopic band ligation for weight loss is a new procedure that may help in the management of obesity. The procedure was safe and cost-effective; however, more studies are needed to assess the effectiveness and safety of band ligations in the management of obesity.

References

1. Abeid Mohamed, Kaddah Tarek. Endoscopic band ligation for weight loss. Endoscopy 2021; 53: E287–E288.

Introduction

Collagenous colitis (CC) and lymphocytic colitis (LC), the two main subtypes of microscopic colitis (MC), are chronic inflammatory diseases of the colon of unknown etiology. Colonic barrier dysfunction has been identified in patients with MC. However, whether molecular and structural alterations underlie an aberrant barrier in MC remains to be defined.

Aims & Methods

To identify the molecular pathways involved in the colonic epithelial brush border structure and its ultrastructural alterations in MC. Total RNA and protein were obtained from sigmoid mucosal biopsies of healthy controls (Hc) (N=11), patients with active diarrhoea predominant irritable bowel syndrome (IBS-D) patients (N=13), and active newly diagnosed naive of treatment MC patients (N=12 CC and N=12 LC). Transcriptomic and proteomic analyses were performed by RNAseq analysis and liquid chromatography mass spectrometry, respectively. Additionally, in a subset of patients (N=8 CC, N=8 LC, N=8 IBS-D and N=8 Hc) sigmoid biospies were collected and processed for scanning and transmission electron microscopy (SEM and TEM, respectively), to perform a qualitative and quantitative assessment of the colonic epithelium. Integrated data assessment was performed to explore biological and molecular functions.

Results

By RNA-Seq enrichment study, three microvilli-related pathways (organization, regulation of microvilli organization and length) were significantly enriched in the colonic mucosa of CC patients compared to LC, IBS-D and Hc. The integrated multi-omic analysis identified 28 genes with a significant positive correlation between RNA expression and its corresponding protein expression, (4 genes with a strong correlation (r>0.7, p<0.05) and 21 genes with a moderate correlation (0.3<r<0.7, p<0.05)), which were related to each other at the network level by string database analysis. Reduced expression of the microvilli proteins, was observed in CC compared to Hc, IBS-D and LC patients. Reduced expression of the actin-binding proteins, was also observed in CC. Moreover, decreased protein expression and an increased expression of proteins in the actin-membrane junction, were observed in CC and LC. Ultrastructural observation revealed that microvilli on the colonic surface of MC patients were more scattered, irregular and shorter in MC than IBS-D and Hc. Furthermore, the number of microvilli per colonocyte length (microvilli/um) was lower in CC (3.7[2.8-5.3], p<0.0001) and LC patients (5.2[4.0-6.6], p=0.01) compared to Hc (7.5[6.6-8.7]). Similarly, microvilli length was also reduced in CC (0.5[0.4-0.8], p=0.0003) and LC (0.6[0.4-1.1], p=0.04) patients compared to Hc (1.1[1.0-1.4]). No differences in the number and length of microvilli were observed between IBS-D and Hc groups.

Conclusion

Dysregulated brush border molecular pathways underlie epithelial colonic dysfunction in MC compared to Hc and IBS-D patients at both molecular and ultrastructural levels. These previously undescribed data open new perspectives in defining the pathophysiological mechanisms of MC, especially in CC. Given the fundamental role of the brush border in maintaining intestinal homeostasis and even water absorption, further understanding of these mechanisms may have significant diagnostic and therapeutic implications for MC.

Disclosure

Dr Javier Santos has served as consultant for Noventure SL, Devintecpharma, Reckitt, Ipsen, Aboca & Pileje and discloses present and past recent scientific collaborations with Salvat, Norgine, Alfa-Sigma, Cosmo, Adare, Ordesa and Danone that do not constitute a conflict of interest in developing the content of the present manuscript.